Adipose-Derived Stem Cell Exosomes in Diabetic Wound Repair: Molecular Crosstalk, Bioengineering Strategies, and Translational Challenges.

Diabetic wounds are sustained by persistent inflammation, impaired angiogenesis, abnormal extracellular matrix (ECM) remodeling, and delayed re-epithelialization. Adipose-derived stem cell exosomes (ADSC-Exos) offer a cell-free strategy because their multicomponent cargo can modulate immune responses, vascular regeneration, fibroblast activity, and epidermal repair. Mechanistic studies suggest that ADSC-Exos promote macrophage immunometabolic reprogramming, restore pro-angiogenic signaling, improve matrix homeostasis, and protect keratinocytes from oxidative injury. Engineering approaches and biomaterial-based delivery systems may further improve local retention, controlled release, and therapeutic activity. Distinct from existing ADSC-Exos reviews, this review adopts a pathology-to-translation framework that connects the major pathological features of diabetic wounds with ADSC-Exos mechanisms, engineering strategies, delivery optimization, and clinical translation. Particular emphasis is placed on donor- and process-dependent heterogeneity, potency assessment, GMP-compatible manufacturing, biodistribution, long-term safety, and regulation. Overall, ADSC-Exos represent a mechanistically compelling preclinical platform, but clinical translation will require reproducible product quality, standardized potency criteria, scalable manufacturing, and rigorous clinical validation.